Objective To establish a sensitive and accurate gas chromatography-mass spectrometry method for determination of quinolinic acid in rat serum.Methods The objective compound was purified and derivatized to its dihexafluoroisopropyl ester before quantitative determination by scanning method and quantitative determination by SIM method.Results The endogenous substances in serum had no interference on the measurement of quinolinic acid in the sample.Assay linearity was obtained in the range of 0.05-20 ?mol/L with limit of quantitation(LOQ)of 0.05 ?mol/L.The intra-day relative standard deviation(RSD)was lower than 15%.The inter-day relative standard deviation was lower than 12%.Conclusion It is a sensitive,accurate and convenient method.The dihexafluoroisopropyl ester of quinolinic acid is quite stable,but the serum should not be preserved for a long time before derivation.

Objective To investigate the role of famesoid X receptor (FXR) and its downstream molecules small heterodimer partner (SHP),UDP-glucuronosyltransferase 2B4 (UGT2B4),and bile salt export pump (BSEP) in rats with acute cholestatic hepatitis.Methods A total of 20 Sprague-Dawley rats were randomly divided into normal control group and model group,with 10 rats in each group.The rats in the model group were given a single dose (50 mg/kg) of α-naphthyl isothiocyanate by gavage to establish the animal model of acute cholestatic hepatitis.Quantitative real-time PCR was used to measure the mRNA expression of FXR,UGT2B4,and BSEP in liver tissue at 48 hours after gavage.An automatic biochemical analyzer was used to measure the serum levels of total bilirubin,direct bilirubin,alanine aminotransferase,total bile acid,aspartate aminotransferase,alkaline phosphatase,and γ-glutamyl transferase.The independent samples t-test was used for comparison of means between groups.Results The model group had significantly lower mRNA expression of FXR,SHP,UGT2B4,and BSEP in liver tissue than the normal control group (0.152 ± 0.088/0.559 ±0.194/0.177 ± 0.039/0.561 ± 0.123 vs 1.137 ± 0.215/1.512 ± 0.309/2.394 ± 0.462/1.631 ± 0.376,t =13.408,8.260,15.121,and 8.553,all P ＜ 0.05).The model group had significantly higher liver fumction parameters than the normal control group (all P ＜ 0.01).Conclusion FXR,SHP,UGT2B4,and BSEP are involved in the development of acute cholestatic hepatitis.Reduced expression of FXR may cause reduced expression of downstream SHP,UGT2B4,and BSEP,increase the synthesis of bile acid,weaken detoxicating and transporting functions,and thus mediate the development of cholestatic hepatitis.

Objective To construct and validate a risk prediction model for delayed healing of venous leg ulcer(VLU),so as to provide a reference basis for early identification of people at high risk of delayed healing.Methods Using a convenience sampling method,331 VLU patients attending vascular surgery departments in 2 tertiary A hospitals in Sichuan Province from January 2018 to December 2022 were selected as a modeling group and an internal validation group,and 112 patients admitted to another tertiary A hospital were selected as an external validation group.Risk factors for delayed healing in VLU patients were screened using univariate analysis,LASSO regression,and multivariate logistic regression analysis,and a risk prediction model was constructed using R software,and the predictive effects of the models were examined using the area under the receiver operating characteristic curve,the Hosmer-Lemeshow test,decision curve,and the bootstrap resampling for internal validation and spatial external validation were performed,respectively.Results The predictors that ultimately entered the prediction model were diabetes(OR=4.752),deep vein thrombosis(OR=4.104),lipodermatosclerosis(OR=5.405),ulcer recurrence(OR=3.239),and ankle mobility(OR=5.520).The model had good discrimination(AUC:0.819 for internal validation and 0.858 for external validation),calibration(Hosmer-Lemeshow test:χ2=13.517,P=0.095 for internal validation and χ2=3.375,P=0.909 for external validation)and clinical validity.Conclusion The model constructed in this study has good differentiation and calibration,and it can effectively predict people at high risk of delayed healing of VLU,which facilitates targeted clinical interventions to improve ulcer outcomes and reduce the risk of delayed ulcer healing.